Different care mode alter composition and function of gut microbiota in cerebral palsy children.

Introduction: Specialized care is essential for the recovery of children with cerebral palsy (CP). This study investigates how different care modes impact the gut microbiota. Methods: Fecal samples from 32 children were collected, among whom those cared for by family (n = 21) were selected as the observation group, and those cared for by children's welfare institutions (n = 11) were selected as the control group (registration number of LGFYYXLL-024). The gut microbiota profiles were analyzed. Results: There was no significant difference in the α-diversity of the gut microbiota and the abundance at the phylum level. However, at the genus level, the observation group showed a significant increase in the abundance of butyrate-producing bacteria Bacteroides and Lachnospiracea incertae sedis (P < 0.05), and a significant decrease in the abundance of opportunistic pathogens Prevotella, Clostridium cluster IV, Oscillibacter, and Fusobacterium (P < 0.05). Additionally, lipid metabolism, carbohydrate metabolism, transcription, cellular processes and signaling, and membrane transport were significantly upregulated in the observation group. Lipid metabolism was positively correlated with Bacteroides and Lachnospiracea incertae sedis, indicating a positive impact of the family-centered care mode on bacterial metabolism processes. Discussion: This study highlights that the family-centered care mode had a positive impact on the composition and function of the gut microbiota. The study provides valuable insights into the relationship between care mode and gut microbiota, which can inspire the development of interventions for cerebral palsy.

Reconstituting gut microbiota-colonocyte interactions reverses diet-induced cognitive deficits: The beneficial of eucommiae cortex polysaccharides.

Rationale: Consumption of a high-fat diet (HFD) has been implicated in cognitive deficits and gastrointestinal dysfunction in humans, with the gut microbiota emerging as a pivotal mediator of these diet-associated pathologies. The introduction of plant-based polysaccharides into the diet as a therapeutic strategy to alleviate such conditions is gaining attention. Nevertheless, the mechanistic paradigm by which polysaccharides modulate the gut microbiota remains largely undefined. This study investigated the mechanisms of action of Eucommiae cortex polysaccharides (EPs) in mitigating gut dysbiosis and examined their contribution to rectifying diet-related cognitive decline. Methods: Initially, we employed fecal microbiota transplantation (FMT) and gut microbiota depletion to verify the causative role of changes in the gut microbiota induced by HFD in synapse engulfment-dependent cognitive impairments. Subsequently, colonization of the gut of chow-fed mice with Escherichia coli (E. coli) from HFD mice confirmed that inhibition of Proteobacteria by EPs was a necessary prerequisite for alleviating HFD-induced cognitive impairments. Finally, supplementation of HFD mice with butyrate and treatment of EPs mice with GW9662 demonstrated that EPs inhibited the expansion of Proteobacteria in the colon of HFD mice by reshaping the interactions between the gut microbiota and colonocytes. Results: Findings from FMT and antibiotic treatments demonstrated that HFD-induced cognitive impairments pertaining to neuronal spine loss were contingent on gut microbial composition. Association analysis revealed strong associations between bacterial taxa belonging to the phylum Proteobacteria and cognitive performance in mice. Further, introducing E. coli from HFD-fed mice into standard diet-fed mice underscored the integral role of Proteobacteria proliferation in triggering excessive synaptic engulfment-related cognitive deficits in HFD mice. Crucially, EPs effectively counteracted the bloom of Proteobacteria and subsequent neuroinflammatory responses mediated by microglia, essential for cognitive improvement in HFD-fed mice. Mechanistic insights revealed that EPs promoted the production of bacteria-derived butyrate, thereby ameliorating HFD-induced colonic mitochondrial dysfunction and reshaping colonocyte metabolism. This adjustment curtailed the availability of growth substrates for facultative anaerobes, which in turn limited the uncontrolled expansion of Proteobacteria. Conclusions: Our study elucidates that colonocyte metabolic disturbances, which promote Proteobacteria overgrowth, are a likely cause of HFD-induced cognitive deficits. Furthermore, dietary supplementation with EPs can rectify behavioral dysfunctions associated with HFD by modifying gut microbiota-colonocyte interactions. These insights contribute to the broader understanding of the modulatory effects of plant prebiotics on the microbiota-gut-brain axis and suggest a potential therapeutic avenue for diet-associated cognitive dysfunction.

Broadening horizons: intestinal microbiota as a novel biomarker and potential treatment for hypertensive disorders of pregnancy.

Hypertensive disorders of pregnancy (HDP) are severe complications of pregnancy with high morbidity and are a major cause of increased maternal and infant morbidity and mortality. Currently, there is a lack of effective early diagnostic indicators and safe and effective preventive strategies for HDP in clinical practice, except for monitoring maternal blood pressure levels, the degree of proteinuria, organ involvement and fetal conditions. The intestinal microbiota consists of the gut flora and intestinal environment, which is the largest microecosystem of the human body and participates in material and energy metabolism, gene expression regulation, immunity regulation, and other functions. During pregnancy, due to changes in hormone levels and altered immune function, the intestinal microecological balance is affected, triggering HDP. A dysregulated intestinal microenvironment influences the composition and distribution of the gut flora and changes the intestinal barrier, driving beneficial or harmful bacterial metabolites and inflammatory responses to participate in the development of HDP and promote its malignant development. When the gut flora is dysbiotic and affects blood pressure, supplementation with probiotics and dietary fiber can be used to intervene. In this review, the interaction between the intestinal microbiota and HDP was investigated to explore the feasibility of the gut flora as a novel biomarker of HDP and to provide a new strategy and basis for the prevention and treatment of clinical HDP.

Host genetics and gut microbiota synergistically regulate feed utilization in egg-type chickens.

BACKGROUND: Feed efficiency is a crucial economic trait in poultry industry. Both host genetics and gut microbiota influence feed efficiency. However, the associations between gut microbiota and host genetics, as well as their combined contributions to feed efficiency in laying hens during the late laying period, remain largely unclear. METHODS: In total, 686 laying hens were used for whole-genome resequencing and liver transcriptome sequencing. 16S rRNA gene sequencing was conducted on gut chyme (duodenum, jejunum, ileum, and cecum) and fecal samples from 705 individuals. Bioinformatic analysis was performed by integrating the genome, transcriptome, and microbiome to screen for key genetic variations, genes, and gut microbiota associated with feed efficiency. RESULTS: The heritability of feed conversion ratio (FCR) and residual feed intake (RFI) was determined to be 0.28 and 0.48, respectively. The ileal and fecal microbiota accounted for 15% and 10% of the FCR variance, while the jejunal, cecal, and fecal microbiota accounted for 20%, 11%, and 10% of the RFI variance. Through SMR analysis based on summary data from liver eQTL mapping and GWAS, we further identified four protein-coding genes, SUCLA2, TNFSF13B, SERTM1, and MARVELD3, that influence feed efficiency in laying hens. The SUCLA2 and TNFSF13B genes were significantly associated with SNP 1:25664581 and SNP rs312433097, respectively. SERTM1 showed significant associations with rs730958360 and 1:33542680 and is a potential causal gene associated with the abundance of Corynebacteriaceae in feces. MARVELD3 was significantly associated with the 1:135348198 and was significantly correlated with the abundance of Enterococcus in ileum. Specifically, a lower abundance of Enterococcus in ileum and a higher abundance of Corynebacteriaceae in feces were associated with better feed efficiency. CONCLUSIONS: This study confirms that both host genetics and gut microbiota can drive variations in feed efficiency. A small portion of the gut microbiota often interacts with host genes, collectively enhancing feed efficiency. Therefore, targeting both the gut microbiota and host genetic variation by supporting more efficient taxa and selective breeding could improve feed efficiency in laying hens during the late laying period.

Gut microbiota-derived Metabolite, Shikimic Acid, inhibits vascular smooth muscle cell proliferation and migration.

Gut microbiota dysbiosis is linked to vascular wall disease, but the mechanisms by which gut microbiota cross-talk with the host vascular cells remain largely unknown. Shikimic acid (SA) is a biochemical intermediate synthesized in plants and microorganisms, but not mammals. Surprisingly, recent metabolomic profiling data demonstrate that SA is detectable in human and murine blood. In this study, analyzing data from germ-free rats, we provide evidence in support of SA as a bona fide gut microbiota-derived metabolite, emphasizing its biological relevance. Since vascular cells are the first cells exposed to circulating metabolites, in this study, we examined, for the first time, the effects and potential underlying molecular mechanisms of SA on vascular smooth muscle cell (VSMC) proliferation and migration, which play a key role in occlusive vascular diseases, such as post-angioplasty restenosis and atherosclerosis. We found that SA inhibits the proliferation and migration of human coronary artery SMCs. At the molecular level, unexpectedly, we found that SA activates, rather than inhibits, multiple pro-mitogenic signaling pathways in VSMCs, such as ERK1/2, AKT, and mTOR/p70S6K. Conversely, we found that SA activates the anti-proliferative AMP-activated protein kinase (AMPK) in VSMCs, a key cellular energy sensor and regulator. However, loss-of-function experiments demonstrate that AMPK does not mediate the inhibitory effects of SA on VSMC proliferation. In conclusion, these studies demonstrate that a microbiota-derived metabolite, SA, inhibits VSMC proliferation and migration in vitro and prompt further evaluation of the possible underlying molecular mechanisms and the potential protective role in VSMC-related vascular wall disease in vivo.

Pathophysiological and Clinical Potential of Human Microbiome: Microbe-based Therapeutic Insights.

The human microbiota represents the community and diverse population of microbes within the human body, which comprises approximately 100 trillion micro-organisms. They exist in the human gastrointestinal tract and various other organs and are now considered virtual body organs. It is mainly represented by bacteria but also includes viruses, fungi, and protozoa. Although there is a heritable component to the gut microbiota, environmental factors related to diet, drugs, and anthropometry determine the composition of the microbiota. Besides the gastrointestinal tract, the human body also harbours microbial communities in the skin, oral and nasal cavities, and reproductive tract. The current review demonstrates the role of gut microbiota and its involvement in processing food, drugs, and immune responses. The discussion focuses on the implications of human microbiota in developing several diseases, such as gastrointestinal infections, metabolic disorders, malignancies, etc., through symbiotic relationships. The microbial population may vary depending on the pathophysiological condition of an individual and thus may be exploited as a therapeutic and clinical player. Further, we need a more thorough investigation to establish the correlation between microbes and pathophysiology in humans and propose them as potential therapeutic targets.

Effects of fructan and gluten on gut microbiota in individuals with self-reported non-celiac gluten/wheat sensitivity-a randomised controlled crossover trial.

BACKGROUND: Individuals with non-celiac gluten/wheat sensitivity (NCGWS) experience improvement in gastrointestinal symptoms following a gluten-free diet. Although previous results have indicated that fructo-oligosaccharides (FOS), a type of short-chain fructans, were more likely to induce symptoms than gluten in self-reported NCGWS patients, the underlying mechanisms are unresolved. METHODS: Our main objective was therefore to investigate whether FOS-fructans and gluten affect the composition and diversity of the faecal microbiota (16S rRNA gene sequencing), faecal metabolites of microbial fermentation (short-chain fatty acids [SCFA]; gas chromatography with flame ionization detector), and a faecal biomarker of gut inflammation (neutrophil gelatinase-associated lipocalin, also known as lipocalin 2, NGAL/LCN2; ELISA). In the randomised double-blind placebo-controlled crossover study, 59 participants with self-reported NCGWS underwent three different 7-day diet challenges with gluten (5.7 g/day), FOS-fructans (2.1 g/day), and placebo separately (three periods, six challenge sequences). RESULTS: The relative abundances of certain bacterial taxa were affected differently by the diet challenges. After the FOS-fructan challenge, Fusicatenibacter increased, while Eubacterium (E.) coprostanoligenes group, Anaerotruncus, and unknown Ruminococcaceae genera decreased. The gluten challenge was primarily characterized by increased abundance of Eubacterium xylanophilum group. However, no differences were found for bacterial diversity (α-diversity), overall bacterial community structure (ß-diversity), faecal metabolites (SCFA), or NGAL/LCN2. Furthermore, gastrointestinal symptoms in response to FOS-fructans were generally not linked to substantial shifts in the gut bacterial community. However, the reduction in E. coprostanoligenes group following the FOS-fructan challenge was associated with increased gastrointestinal pain. Finally, correlation analysis revealed that changes in gastrointestinal symptoms following the FOS-fructan and gluten challenges were linked to varying bacterial abundances at baseline. CONCLUSIONS: In conclusion, while FOS-fructans induced more gastrointestinal symptoms than gluten in the NCGWS patients, we did not find that substantial shifts in the composition nor function of the faecal microbiota could explain these differences in the current study. However, our results indicate that individual variations in baseline bacterial composition/function may influence the gastrointestinal symptom response to both FOS-fructans and gluten. Additionally, the change in E. coprostanoligenes group, which was associated with increased symptoms, implies that attention should be given to these bacteria in future trials investigating the impact of dietary treatments on gastrointestinal symptoms. TRIAL REGISTRATION: Clinicaltrials.gov as NCT02464150.

Berberine and magnolol exert cooperative effects on ulcerative colitis in mice by self-assembling into carrier-free nanostructures.

The risk of ulcerative colitis (UC) is increasing worldwide with limited success using classical drugs, which has underscored the development of novel agents. Recently, carrier-free molecular assembly has been proven to be an effective drug delivery system, but it has yet to be examined for UC drug development using phytochemicals. Based on traditional Chinese medicine compatibility and potential medicinal uses, a pair of natural compounds, berberine (BBR) and magnolol (MAG), were found to self-assemble into nanostructures in aqueous solutions. Spectral analysis revealed that the assembly mechanisms of BBR and MAG were mediated through charge interactions and π-π stacking. Pharmacokinetic studies and animal imaging showed that BBR-MAG self-assembly (BM) effectively promoted the oral bioavailability and biodistribution of BBR in the colon. BM exhibited superior effects in regulating inflammatory factors, maintaining colon barrier integrity, and regulating gut microbiota in a dextran sulfate sodium salt-induced colitis mouse model. Additionally, no apparent signs of toxicity were observed, suggesting that BM has a favorable safety profile. This study presents a new strategy for UC management and highlights the cooperative effects of combined phytochemicals.

Integrative microbiome and metabolome profiles reveal the impacts of periodontitis via oral-gut axis in first-trimester pregnant women.

BACKGROUND: Periodontitis results from host-microbe dysbiosis and the resultant dysregulated immunoinflammatory response. Importantly, it closely links to numerous systemic comorbidities, and perplexingly contributes to adverse pregnancy outcomes (APOs). Currently, there are limited studies on the distal consequences of periodontitis via oral-gut axis in pregnant women. This study investigated the integrative microbiome-metabolome profiles through multi-omics approaches in first-trimester pregnant women and explored the translational potentials. METHODS: We collected samples of subgingival plaques, saliva, sera and stool from 54 Chinese pregnant women at the first trimester, including 31 maternal periodontitis (Perio) subjects and 23 Non-Perio controls. By integrating 16S rRNA sequencing, untargeted metabolomics and clinical traits, we explored the oral-gut microbial and metabolic connection resulting from periodontitis among early pregnant women. RESULTS: We demonstrated a novel bacterial distinguisher Coprococcus from feces of periodontitis subjects in association with subgingival periodontopathogens, being different from other fecal genera in Lachnospiraceae family. The ratio of fecal Coprococcus to Lachnoclostridium could discriminate between Perio and Non-Perio groups as the ratio of subgingival Porphyromonas to Rothia did. Furthermore, there were differentially abundant fecal metabolic features pivotally enriched in periodontitis subjects like L-urobilin and kynurenic acid. We revealed a periodontitis-oriented integrative network cluster, which was centered with fecal Coprococcus and L-urobilin as well as serum triglyceride. CONCLUSIONS: The current findings about the notable influence of periodontitis on fecal microbiota and metabolites in first-trimester pregnant women via oral-gut axis signify the importance and translational implications of preconceptional oral/periodontal healthcare for enhancing maternal wellbeing.

Modulations in gastrointestinal microbiota during postpartum period fulfill energy requirements and maintain health of lactating Tibetan cattle.

Introduction: Postpartum period of dairy cattle is an important phase of their life mainly associated with the changes in physiology, rumen function, and energy metabolism. Studies have shown that gut microbial composition undergoes drastic changes during the postpartum period. However, little is known about the temporal variations in digestive tract microbiota in postpartum Tibetan cattle. The aim of this study was to investigate the temporal variations in blood metabolites, ruminal fermentation, and microbial community of oral, rumen, and gut in lactating Tibetan cattle during postpartum. Methods: We collected blood, saliva, rumen fluid, and fecal samples from lactating Tibetan cattle during 1st week (1 W), the 2nd week (2 W), the 1st month (1 M), and the 2nd month (2 M) of the postpartum period. The microbiota of saliva, rumen fluid, and fecal samples were assessed using 16S rRNA sequencing. The rumen volatile fatty acid and blood parameters were also quantified. Results: The content of volatile fatty acids (VFAs) and blood parameters showed opposite tendency to each other and reached to stability at 2 M. Rumen microbiota showed the highest alpha diversity compared to other two sites. At phylum level, the oral cavity was dominated by Proteobacteria, while most dominant phylum in rumen and feces were Firmicutes and Bacteroidetes, respectively. The dominant genera in oral cavity were Moraxella and Bibersteinia, while genera Prevotella 1 and Ruminococcaceae UCG-005 were dominant in rumen and fecal samples, respectively. Discussion: Microbial network analysis revealed that most of the active genera in all networks belonged to phylum Firmicutes, indicating the importance of this phyla during postpartum period of lactating cattle. The functional analysis revealed distinct division of labor among three gastrointestinal sites associated with defense, fatty acid synthesis, and maintaining health of host. All in all, our findings provide insights into the metabolic and microbial changes of lactating Tibetan cattle and help to the improvement of the management strategies.

Global transcriptomic network analysis of the crosstalk between microbiota and cancer-related cells in the oral-gut-lung axis.

Background: The diagnosis and treatment of lung, colon, and gastric cancer through the histologic characteristics and genomic biomarkers have not had a strong impact on the mortality rates of the top three global causes of death by cancer. Methods: Twenty-five transcriptomic analyses (10 lung cancer, 10 gastric cancer, and 5 colon cancer datasets) followed our own bioinformatic pipeline based on the utilization of specialized libraries from the R language and DAVID´s gene enrichment analyses to identify a regulatory metafirm network of transcription factors and target genes common in every type of cancer, with experimental evidence that supports its relationship with the unlocking of cell phenotypic plasticity for the acquisition of the hallmarks of cancer during the tumoral process. The network's regulatory functional and signaling pathways might depend on the constant crosstalk with the microbiome network established in the oral-gut-lung axis. Results: The global transcriptomic network analysis highlighted the impact of transcription factors (SOX4, TCF3, TEAD4, ETV4, and FOXM1) that might be related to stem cell programming and cancer progression through the regulation of the expression of genes, such as cancer-cell membrane receptors, that interact with several microorganisms, including human T-cell leukemia virus 1 (HTLV-1), the human papilloma virus (HPV), the Epstein-Barr virus (EBV), and SARS-CoV-2. These interactions can trigger the MAPK, non-canonical WNT, and IFN signaling pathways, which regulate key transcription factor overexpression during the establishment and progression of lung, colon, and gastric cancer, respectively, along with the formation of the microbiome network. Conclusion: The global transcriptomic network analysis highlights the important interaction between key transcription factors in lung, colon, and gastric cancer, which regulates the expression of cancer-cell membrane receptors for the interaction with the microbiome network during the tumorigenic process.

A role of gut microbiota metabolites in HLA-E and NKG2 blockage immunotherapy against tumors: new insights for clinical application.

One of major breakthroughs in immunotherapy against tumor is from blocking immune checkpoint molecules on tumor and reactive T cells. The development of CTLA-4 and PD-1 blockage antibodies has triggered to search for additional effective therapeutic strategies. This causes recent findings that blocking the interaction of checkpoint molecule NKG2A in NK and CD8 T cells with HLA-E in tumors is effective in defensing tumors. Interestingly, gut microbiota also affects this immune checkpoint immunotherapy against tumor. Gut microbiota such as bacteria can contribute to the regulation of host immune response and homeostasis. They not only promote the differentiation and function of immunosuppressive cells but also the inflammatory cells through the metabolites such as tryptophan (Trp) and bile acid (BA) metabolites as well as short chain fatty acids (SCFAs). These gut microbiota metabolites (GMMs) educated immune cells can affect the differentiation and function of effective CD8 and NK cells. Notably, these metabolites also directly affect the activity of CD8 and NK cells. Furthermore, the expression of CD94/NKG2A in the immune cells and/or their ligand HLA-E in the tumor cells is also regulated by gut microbiota associated immune factors. These findings offer new insights for the clinical application of gut microbiota in precise and/or personalized treatments of tumors. In this review, we will discuss the impacts of GMMs and GMM educated immune cells on the activity of effective CD8 and NK cells and the expression of CD94/NKG2A in immune cells and/or their ligand HLA-E in tumor cells.

East meets west: integrating Yin-Yang theory with immunology teaching.

This perspective article delves into a novel integration of Yin-Yang theory-an ancient Chinese philosophical cornerstone-with the sophisticated realm of immunology. Given the intricate concepts inherent in immunology, many students find it challenging to comprehend the delicate mechanisms governing immune equilibrium and regulation. Given the deep-rooted understanding of Yin-Yang theory among Chinese students, we advocate for an educational strategy that contextualizes the concept of immune equilibrium within the framework of Yin-Yang, thereby offering a more intuitive and engaging learning experience. This method not only capitalizes on the cultural significance of Yin-Yang, but also corresponds to its principles of equilibrium and harmony, thus mirroring the homeostatic essence of immune responses. This article critically assesses this technique's capacity to bolster immune comprehension amongst Chinese students, while also considering its limitations. Despite these limitations, the fusion of these seemingly divergent fields holds substantial promise for augmenting immunology education, promoting critical thinking, and advancing cross-cultural academic discourse. The amalgamation of age-old philosophical insights with modern scientific exploration prompts a reassessment of educational methodologies within immunology, underscoring a novel pedagogical approach that bridges traditional wisdom with contemporary scientific education.

Next generation probiotics for human health: An emerging perspective.

Over recent years, the scientific community has acknowledged the crucial role of certain microbial strains inhabiting the intestinal ecosystem in promoting human health, and participating in various beneficial functions for the host. These microorganisms are now referred to as next-generation probiotics and are currently considered as biotherapeutic products and food or nutraceutical supplements. However, the majority of next-generation probiotic candidates pose nutritional demands and exhibit high sensitivity towards aerobic conditions, leading to numerous technological hurdles in large-scale production. This underscores the need for the development of suitable delivery systems capable of enhancing the viability and functionality of these probiotic strains. Currently, potential candidates for next generation probiotics (NGP) are being sought among gut bacteria linked to health, which include strains from the genera Bacteroids, Faecalibacterium, Akkermansia and Clostridium. In contrast to Lactobacillus spp. and Bifidobacterium spp., NGP, particularly Bacteroids spp. and Clostridium spp., appear to exhibit greater ambiguity regarding their potential to induce infectious diseases. The present review provides a comprehensive overview of NGPs in terms of their health beneficial effects, regulation framework and risk assessment targeting relevant criteria for commercialization in food and pharmaceutical markets.

Commensal bacteria exacerbate seizure-like phenotypes in Drosophila voltage-gated sodium channel mutants.

Mutations in voltage-gated sodium (Nav) channels, which are essential for generating and propagating action potentials, can lead to serious neurological disorders, such as epilepsy. However, disease-causing Nav channel mutations do not always result in severe symptoms, suggesting that the disease conditions are significantly affected by other genetic factors and various environmental exposures, collectively known as the "exposome". Notably, recent research emphasizes the pivotal role of commensal bacteria in neural development and function. Although these bacteria typically benefit the nervous system under normal conditions, their impact during pathological states remains largely unknown. Here, we investigated the influence of commensal microbes on seizure-like phenotypes exhibited by paraShu-a gain-of-function mutant of the Drosophila Nav channel gene, paralytic. Remarkably, the elimination of endogenous bacteria considerably ameliorated neurological impairments in paraShu. Consistently, reintroducing bacteria, specifically from the Lactobacillus or Acetobacter genera, heightened the phenotypic severity in the bacteria-deprived mutants. These findings posit that particular native bacteria contribute to the severity of seizure-like phenotypes in paraShu. We further uncovered that treating paraShu with antibiotics boosted Nrf2 signaling in the gut, and that global Nrf2 activation mirrored the effects of removing bacteria from paraShu. This raises the possibility that the removal of commensal bacteria suppresses the seizure-like manifestations through augmented antioxidant responses. Since bacterial removal during development was critical for suppression of adult paraShu phenotypes, our research sets the stage for subsequent studies, aiming to elucidate the interplay between commensal bacteria and the developing nervous system in conditions predisposed to the hyperexcitable nervous system.

Drosophila HNF4 acts in distinct tissues to direct a switch between lipid storage and export in the gut.

Nutrient digestion, absorption, and export must be coordinated in the gut to meet the nutritional needs of the organism. We used the Drosophila intestine to characterize the mechanisms that coordinate the fate of dietary lipids. We identified enterocytes specialized in absorbing and exporting lipids to peripheral organs. Distinct hepatocyte-like cells, called oenocytes, communicate with these enterocytes to adjust intestinal lipid storage and export. A single transcription factor, Drosophila hepatocyte nuclear factor 4 (dHNF4), supports this gut-liver axis. In enterocytes, dHNF4 maximizes dietary lipid export by preventing their sequestration in cytoplasmic lipid droplets. In oenocytes, dHNF4 promotes the expression of the insulin antagonist ImpL2 to activate Foxo and suppress lipid retention in enterocytes. Disruption of this switch between lipid storage and export is associated with intestinal inflammation, suggesting a lipidic origin for inflammatory bowel diseases. These studies establish dHNF4 as a central regulator of intestinal metabolism and inter-organ lipid trafficking.

Postbiotic impact on host metabolism and immunity provides therapeutic potential in metabolic disease.

The gut microbiota influences aspects of metabolic disease, including tissue inflammation, adiposity, blood glucose, insulin, and endocrine control of metabolism. Prebiotics or probiotics are often sought to combat metabolic disease. However, prebiotics lack specificity and can have deleterious bacterial community effects. Probiotics require live bacteria to find a colonization niche sufficient to influence host immunity or metabolism. Postbiotics encompass bacterial-derived components and molecules, which are well-positioned to alter host immunometabolism without relying on colonization efficiency or causing widespread effects on the existing microbiota. Here, we summarize the potential for beneficial and detrimental effects of specific postbiotics related to metabolic disease and the underlying mechanisms of action. Bacterial cell wall components such as lipopolysaccharides, muropeptides, lipoteichoic acids and flagellin have context-dependent effects on host metabolism by engaging specific immune responses. Specific types of postbiotics within broad classes of compounds such as lipopolysaccharides, muropeptides can have opposing effects on endocrine control of host metabolism where certain postbiotics are insulin sensitizers and others promote insulin resistance. Bacterial metabolites such as short chain fatty acids, bile acids, lactate, glycerol, succinate, ethanolamine, and ethanol can be substrates for host metabolism. Postbiotics can fuel host metabolic pathways directly or influence endocrine control of metabolism through immunomodulation or mimicking host-derived hormones. The interaction of postbiotics in the host-microbe relationship should be considered during metabolic inflammation and metabolic disease.

Fusarium graminearum spores disrupt gut microbiota and metabolome via the lung-gut axis in mice.

Fusarium graminearum, the primary pathogen responsible for wheat Fusarium head blight, can induce pulmonary damage through its spores. However, the detailed mechanism by which these spores cause intestinal injury is not yet fully understood. This study aimed to investigate the impact of exposure to fungal spores on the intestinal microbiota using a mice model that mimics the effects of fusarium graminearum spores on the gut microbiota and its metabolic profile. The study utilized 16S rRNA sequencing and metabolomics methodologies to analyze the contents of the cecum and feces in mice. The results showed that exposure to fungal spores led to significant changes in the composition of the intestinal microbiota in mice, characterized by an increase in Akkermansia and Staphylococcus populations. A non-targeted metabolomics analysis identified 316 metabolites associated with various metabolic pathways, particularly galactose metabolism. Pre-exposure to antibiotics before fungal spore exposure resulted in a decrease in the metabolic capacity of the intestinal microbiota in mice. This research demonstrates that fusarium graminearum spores can disrupt the intestinal microbiota and metabolome via the lung-gut axis. These findings provide valuable insights into the intestinal damage caused by fungal spores and offer important support for the development of therapeutic strategies for intestinal diseases.

Biomimetic nanoplatform with microbiome modulation and antioxidant functions ameliorating insulin resistance and pancreatic ß-cell dysfunction for T2DM management.

Insulin resistance and pancreatic ß-cell dysfunction are the main pathogenesis of type 2 diabetes mellitus (T2DM). However, insulin therapy and diabetes medications do not effectively solve the two problems simultaneously. In this study, a biomimetic oral hydrogen nanogenerator that leverages the benefits of edible plant-derived exosomes and hydrogen therapy was constructed to overcome this dilemma by modulating gut microbiota and ameliorating oxidative stress and inflammatory responses. Hollow mesoporous silica (HMS) nanoparticles encapsulating ammonia borane (A) were used to overcome the inefficiency of H2 delivery in traditional hydrogen therapy, and exosomes originating from ginger (GE) were employed to enhance biocompatibility and regulate intestinal flora. Our study showed that HMS/A@GE not only considerably ameliorated insulin resistance and liver steatosis, but inhibited the dedifferentiation of islet ß-cell and enhanced pancreatic ß-cell proportion in T2DM model mice. In addition to its antioxidant and anti-inflammatory effects, HMS/A@GE augmented the abundance of Lactobacilli spp. and tryptophan metabolites, such as indole and indole acetic acid, which further activated the AhR/IL-22 pathway to improve intestinal-barrier function and metabolic impairments. This study offers a potentially viable strategy for addressing the current limitations of diabetes treatment by integrating gut-microbiota remodelling with antioxidant therapies.

Naturally Occurring Food Chemical Components and Extraintestinal and Gastrointestinal Symptoms in Adults: A Systematic Review.

OBJECTIVE: This systematic review aims to synthesise existing literature to examine the relationship between natural food chemical components and reported symptoms. DESIGN: A systematic literature review was completed. Databases CINAHL (Ebscohost), Medline (Ovid), Scopus, Informit Health and Google Scholar were searched to identify relevant articles. The population included human studies of adults (≥17 years) and excluded those with IgE-mediate food allergies. Studies examining food chemical components or 'food chemical elimination diets' and symptoms were included. Data was synthesised based on clinical conditions and specific food chemical components examined. The risk of bias was assessed using the Academy of Nutrition and Dietetics 'Quality Criteria Checklist: Primary Research'. RESULTS: Of the 1659 articles retrieved, 21 met inclusion criteria. This included eight randomised controlled trials, four non-randomised controlled trials, four cohort studies with placebo-controlled challenge, one prospective cohort study, three cross sectional cohort studies, one case-controlled study. Available studies support the role of a low-histamine diet for symptoms in chronic urticaria and low-salicylate diet for reducing sino-nasal symptoms in aspirin exacerbated respiratory disease and chronic rhinosinusitis and/or asthma. While further evidence is needed to verify the role of glutamate in respiratory, pain, asthma and gastrointestinal symptoms. CONCLUSIONS: Food chemical elimination diets may improve condition-specific symptoms across the adult cohorts outlined within this review, with the strongest evidence to support the role of a low-histamine diet for management of symptoms in chronic urticaria and a low-salicylate diet in aspirin exacerbated respiratory disease and/or asthma. Further well-designed trials are needed to elucidate the effect of specific natural food chemical components on symptoms. TRIAL REGISTRATION: Systematic review number: CRD42022322511.